In Memoriam: Theodore R. Schrock, M.D.

Inside Surgery Winter-Spring 2016

This issue focuses on how the new Mission Bay hospitals are enhancing surgical care highlighting research and clinical advances in colorectal surgery, surgical oncology, pediatric surgery, and breast care surgery.

Participating in Clinical Trials

Choosing to participate in a clinical trial is an important personal decision. The following frequently asked questions provide detailed information about clinical trials. In addition, it is often helpful to talk to a physician, family members, or friends about deciding to join a trial. After identifying some trial options, the next step is to contact the study research staff and ask questions about specific trials.

What is a clinical trial?

Physicians use clinical research to learn about a new method for treating a medical disease or disorder. A clinical trial is a strictly controlled study in people. Clinical trials are approved and monitored by the UCSF Committee on Human Research.

Medical research studies include only those patients who choose to take part. Patients who are eligible for clinical studies will be counseled about the condition and made aware of all their options. It is important to understand that participation in a clinical study is completely voluntary and the decision to not participate in a study will not affect your medical care.

Why participate in a clinical trial?

Participants in clinical trials can play a more active role in their own health care, gain access to new research treatments before they are widely available, and help others by contributing to medical research.

Who can participate in a clinical trial?

All clinical trials have guidelines about who can participate. Using inclusion/exclusion criteria is an important principle of medical research that helps to produce reliable results. The factors that allow someone to participate in a clinical trial are called "inclusion criteria" and those that disallow someone from participating are called "exclusion criteria".

These criteria are based on such factors as age, gender, the type and stage of a disease, previous treatment history, and other medical conditions. Before joining a clinical trial, a participant must qualify for the study. Some research studies seek participants with illnesses or conditions to be studied in the clinical trial, while others need healthy participants. It is important to note that inclusion and exclusion criteria are not used to reject people personally. Instead, the criteria are used to identify appropriate participants and keep them safe. The criteria help ensure that researchers will be able to answer the questions they plan to study.

What happens during a clinical trial?

The clinical trial process depends on the kind of trial being conducted (See What are the different types of clinical trials?) The clinical trial team includes doctors and nurses as well as social workers and other health care professionals. They check the health of the participant at the beginning of the trial, give specific instructions for participating in the trial, monitor the participant carefully during the trial, and stay in touch after the trial is completed.

Some clinical trials involve more tests and doctor visits than the participant would normally have for an illness or condition. For all types of trials, the participant works with a research team. Clinical trial participation is most successful when the protocol is carefully followed and there is frequent contact with the research staff.

What is informed consent?

Informed consent is the process of learning the key facts about a clinical trial before deciding whether or not to participate. It is also a continuing process throughout the study to provide information for participants. To help someone decide whether or not to participate, the doctors and nurses involved in the trial explain the details of the study. If the participant's native language is not English, translation assistance can be provided.

Then the research team provides an informed consent document that includes details about the study, such as its purpose, duration, required procedures, and key contacts. Risks and potential benefits are explained in the informed consent document. The participant then decides whether or not to sign the document. Informed consent is not a contract, and the participant may withdraw from the trial at any time.

Deciding to Take Part in Clinical Trials

Whenever you need treatment, clinical trials may be an option for you. Choosing to join a clinical trial is something only you, those close to you, and your doctors and nurses can decide together. This section has information you can use when thinking about your treatment choices and making your decision.

Weighing the Pros and Cons

As a treatment option, a clinical trial has possible benefits as well as drawbacks. You may want to discuss the following issues with your doctor and the people close to you.

Possible Benefits

Clinical trials offer high-quality care. If you are in a randomized study and do not receive the new treatment being tested, you will receive the best known standard treatment. This may be as good as, or better than, the new approach.

If a new treatment is proven to work and you are taking it, you may be among the first to benefit.

By looking at the pros and cons of clinical trials and your other treatment choices, you are taking an active role in a decision that affects your life.

You have the chance to help others and improve treatment.

Possible Drawbacks

New treatments under study are not always better than, or even as good as, standard care.

If you receive standard care instead of the new treatment being tested, it may not be as effective as the new approach.

New treatments may have side effects that doctors do not expect or that are worse than those of standard treatment.

Even if a new treatment has benefits, it may not work for you. Even standard treatments, proven effective for many people, do not help everyone.

Health insurance and managed care providers do not always cover all patient care costs in a study. What they cover varies by plan and by study. To find out in advance what costs are likely to be paid in your case, check with your insurance company and talk to a doctor, nurse or social worker from the study. If a new treatment is proven to work and you are taking it, you may be among the first to benefit.

What are side effects and adverse reactions?

Side effects are any undesired actions or effects of the experimental drug or treatment. Negative or adverse effects may include headache, nausea, hair loss, skin irritation, or other physical problems. Experimental treatments must be evaluated for both immediate and long-term side effects.

How is the safety of the participant protected?

The ethical and legal codes that govern medical practice also apply to clinical trials. In addition, most clinical research is federally regulated with built in safeguards to protect the participants. The trial follows a carefully controlled protocol, a study plan which details what researchers will do in the study. As a clinical trial progresses, researchers report the results of the trial at scientific meetings, to medical journals, and to various government agencies. Individual participants' names will remain secret and will not be mentioned in these reports (See Confidentiality Regarding Trial Participants).

What should people consider before participating in a trial?

People should know as much as possible about the clinical trial and feel comfortable asking the members of the health care team questions about it, the care expected while in a trial, and the cost of the trial. The following questions might be helpful for the participant to discuss with the health care team. Some of the answers to these questions are found in the informed consent document.

What is the purpose of the study?

Who is going to be in the study?

Why do researchers believe the experimental treatment being tested may be effective? Has it been tested before?

What kinds of tests and experimental treatments are involved?

How do the possible risks, side effects, and benefits in the study compare with my current treatment?

How might this trial affect my daily life?

How long will the trial last?

Will hospitalization be required?

Who will pay for the experimental treatment?

Will I be reimbursed for other expenses?

What type of long-term follow up care is part of this study?

How will I know that the experimental treatment is working? Will results of the trials be provided to me?

Who will be in charge of my care?

What kind of preparation should a potential participant make for the meeting with the research coordinator or doctor?

Plan ahead and write down possible questions to ask.

Ask a friend or relative to come along for support and to hear the responses to the questions.

Bring a tape recorder to record the discussion to replay later.

Every clinical trial in the U.S. must be approved and monitored by an Institutional Review Board (IRB) to make sure the risks are as low as possible and are worth any potential benefits. An IRB is an independent committee of physicians, statisticians, community advocates, and others that ensures that a clinical trial is ethical and the rights of study participants are protected. All institutions that conduct or support biomedical research involving people must, by federal regulation, have an IRB that initially approves and periodically reviews the research.

Does a participant continue to work with a primary health care provider while in a trial?

Yes. Most clinical trials provide short-term treatments related to a designated illness or condition, but do not provide extended or complete primary health care. In addition, by having the health care provider work with the research team, the participant can ensure that other medications or treatments will not conflict with the protocol.

Can a participant leave a clinical trial after it has begun?

Yes. A participant can leave a clinical trial, at any time. When withdrawing from the trial, the participant should let the research team know about it, and the reasons for leaving the study.

Where do the ideas for trials come from?

Ideas for clinical trials usually come from researchers. After researchers test new therapies or procedures in the laboratory and in animal studies, the experimental treatments with the most promising laboratory results are moved into clinical trials. During a trial, more and more information is gained about an experimental treatment, its risks and how well it may or may not work.

Who sponsors clinical trials?

Clinical trials are sponsored or funded by a variety of organizations or individuals such as physicians, medical institutions, foundations, voluntary groups, and pharmaceutical companies, in addition to federal agencies such as the National Institutes of Health (NIH), the Department of Defense (DOD), and the Department of Veteran's Affairs (VA). Trials can take place in a variety of locations, such as hospitals, universities, doctors' offices, or community clinics.

What is a protocol?

A protocol is a study plan on which all clinical trials are based. The plan is carefully designed to safeguard the health of the participants as well as answer specific research questions. A protocol describes what types of people may participate in the trial; the schedule of tests, procedures, medications, and dosages; and the length of the study. While in a clinical trial, participants following a protocol are seen regularly by the research staff to monitor their health and to determine the safety and effectiveness of their treatment.

What is a placebo?

A placebo is an inactive pill, liquid, or powder that has no treatment value. In clinical trials, experimental treatments are often compared with placebos to assess the experimental treatment's effectiveness. In some studies, the participants in the control group will receive a placebo instead of an active drug or experimental treatment.

What are the different types of clinical trials?

Treatment trials test experimental treatments, new combinations of drugs, or new approaches to surgery or radiation therapy.

Prevention trials look for better ways to prevent disease in people who have never had the disease or to prevent a disease from returning. These approaches may include medicines, vaccines, vitamins, minerals, or lifestyle changes.

Diagnostic trials are conducted to find better tests or procedures for diagnosing a particular disease or condition.

Screening trials test the best way to detect certain diseases or health conditions.

Quality of Life trials (or Supportive Care trials) explore ways to improve comfort and the quality of life for individuals with a chronic illness.

What are the phases of clinical trials?

Clinical trials are conducted in phases. The trials at each phase have a different purpose and help scientists answer different questions: For a treatment to become part of standard treatment, it must first go through 3 or 4 clinical trial phases. Patients do not have to take part in all phases. The early phases make sure the treatment is safe. Later phases show if it works better than the standard treatment.

Number of people who take part

Phase I

In Phase I trials, researchers test an experimental drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

20-80 people

Phase II

In Phase II trials, the experimental study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

100 -300 people

Phase III

In Phase III trials, the experimental study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the experimental drug or treatment to be used safely.

Randomization

Randomization is a process used in some clinical trials to prevent bias. Bias occurs when a trial's results are affected by human choices or other factors not related to the treatments being tested. Randomization helps ensure that unknown factors do not affect trial results.

In a randomized clinical trial, you will be assigned by chance to either a control group or an investigational group.

Randomization is used in all phase III and some phase II trials. These trials are called randomized clinical trials. If you participate in such a trial, you will be assigned by chance to either an investigational group or a control group. Your assignment will be determined with a computer program or table of random numbers.

What is a control or control group?

A control is the standard by which experimental observations are evaluated. In many clinical trials, one group of patients will be given an experimental drug or treatment, while the control group is given either a standard treatment for the illness or a placebo.

If you are assigned to the control group, you will get the most widely accepted treatment (standard treatment).

If you are assigned to the investigational group, you will get the new treatment being tested. Comparing these groups to each other often clearly shows which treatment is more effective or has fewer side effects. If you are thinking about joining a randomized clinical trial, you need to understand that you have an equal chance to be assigned to either one of the groups. The doctor does not choose the group for you.

Will I get a placebo?

A placebo is designed to look like the medicine being tested, but it is not active. Placebos are almost never used in treatment trials. In some cases, a study may compare standard treatment plus a new treatment, to standard treatment plus a placebo. You will be told if the study uses a placebo

What is an "expanded access" protocol?

Most human use of investigational new drugs takes place in controlled clinical trials conducted to assess safety and efficacy of new drugs. Data from the trials can serve as the basis for the drug marketing application. Sometimes, patients do not qualify for these carefully-controlled trials be cause of other health problems, age, or other factors.

For patients who may benefit from the drug use but don't qualify for the trials, FDA regu lations enable manufacturers of investigational new drugs to provide for "expanded access" use of the drug. For example, a treatment IND (Investigational New Drug application) or treatment protocol is a relatively unrestricted study. The primary intent of a treatment IND/protocol is to provide for access to the new drug for people with a life-threatening or serious disease for which there is no good alternative treatment. A secondary purpose for a treatment IND/protocol is to generate additional information about the drug, especially its safety.

Expanded access protocols can be undertaken only if clinical investigators are actively studying the experimental treatment in well-controlled studies, or all studies have been completed. There must be evidence that the drug may be an effective treatment in patients like those to be treated under the protocol. The drug cannot expose patients to unreasonable risks given the severity of the disease to be treated.

Some investigational drugs are available from pharmaceutical manufacturers through expanded access programs listed in ClinicalTrials.gov. Expanded access protocols are generally managed by the manufacturer, with the investigational treatment administered by researchers or doctors in office-based practice. If you or a loved one are interested in treatment with an investigational drug under an expanded access protocol listed in ClinicalTrials.gov, review the protocol eligibility criteria and location information and inquire at the Contact Information number.

Questions to Ask

If you are thinking about taking part in a clinical trial, here are some questions that can help you decide.

About this trial

Why is this trial being done?

Why do the doctors who designed the trial believe that the treatment being studied may be better than the one being used now? Why may it not be better?

How long will I be in the trial?

What kinds of tests and treatments are involved?

What are the possible side effects or risks of the new treatment?

What are the possible benefits?

How will the doctor know if the treatment is working?

Costs

Will I have to pay for any of the treatments or tests?

What costs will my health insurance cover?

Daily life

How could the trial affect my daily life?

How often will I have to come to the hospital or clinic?

Will I have to travel long distances?

Comparing choices

What are my other treatment choices, including standard treatments?

How does the treatment I would receive in this trial compare with the other treatment choices?

Text on this page was reproduced, in whole or in part, from descriptions at http://www.clinicaltrials.gov, and/or National Cancer Institute (NCI) at http://www.cancer.gov/, originator(s) of the content. Any modifications, including explanatory or supplemental material, were added to enhance the reader's understanding.